CRISPR and RNA editing

I find it somewhat satisfying that the field of RNA editing (in the broad sense) which I and my students worked on for so long is contributing, at least linguistically, to one of the most exciting gene modification techniques developed in recent years - CRISPR. Initially Doudna showed that joining two RNAs, one encoding a DNA nuclease and the other a short RNA sequence complementary to the site to be edited produced an RNA that could recognize and modify specific sites in genomic DNA. The mechanism of site specificity was simple base pairing and they used the term "guide RNA or gRNA" to describe this construct. This was the mechanism my lab had discovered in 1990 by which the insertion/deletion of uridine residues at precise sites in the cryptogenes encoded in maxicircle mitochondrial DNA of trypanosomatid parasites was achieved. We coined the term, guide RNA to describe short RNAs encoded mainly by the thousands of catenated minicircles in the kinetoplast mitochondria DNA which could recognize specific sites to be edited and recruit multiple protein complexes that precisely cleaved the mRNA, inserted uridines and then joined the two DNA fragments. Several additional “editing” phenomena were soon discovered that changed C to U in mammalian ApoB mRNA and changed encoded adenosine resides in multiple mammalian mRNAs to inosine, which behaved like guanosine. Again the site specificities, at least in ADAR editing, were determined by the mRNAs encoding complementary sequences in cis which acted by foldback to identify specific sites by base pairing and then recruiting ADAR adenosine deaminase enzymes. In fact, in our RNA editing Gordon Conferences at that time, the term “RNA editing” was used for both the trypanosomatid insertion/deletion of U’s and the method by which precise A’s were changed to G’s (functionally) or C’s to U. And now ADAR and APOBEC editing has solved one of the major problems of the CRISPR system by allowing the efficient production of specific nucleotide changes in mRNAs without non-specific changes elsewhere in the genome.
Truly, the incredible insight of Jim Watson and Francis Crick in their DNA double helix model in 1953 which was based on the base pairing of nucleotides in the two strands led to their understated ending comment in their Nature paper that it has not escaped their attention that this would lead to an elegant mechanism for DNA replication.

A New Old Drug Against an Old Disease - African Trypanosomiasis 

There has been a truly exciting drug development against African trypanosomiasis. The previous arsenical drugs used were either very toxic to the patient and the more recent (2009) combination of nifurtimox-eflornithine (NECT) had to administered as a combination of pills and 14 intravenous infusions. The NECT was not toxic and could kill parasites even after they entered the brain. The down side was that this treatment could not easily be used in rural African villages. The same organization that developed NECT in 2007 rediscovered fexinidazole, a compound that Sanofi had developed as an general antiparasitic drug but had  not pursued it any further. Researchers supported by the Drugs for Neglected Diseases initiative found both in animal models and in humans that this drug  taken orally cured 99% of people in the early bloodstream stage of the disease and 91% of people in  the tertiary stage where the trypanosomes had entered the brain!  The drug was taken through clinical trials and should be approved by the European Medicines Agency for use  in infected humans in the Democratic Republic of the Congo by the end of 2018. This may prove to be the magic bullet against this devastating disease in tropical Africa. I myself hope that resistance will not be rapidly developed. The best way to avoid development of resistance would be to combine another effective drug with fexinidazole, which unfortunately remains to be discovered.

An Interstellar Visitor

Astronomers have long speculated that debris from exoplanet formation could be ejected from another solar system but nothing so far has been observed (if we ignore the domestic molecules formed from elements created by supernova and kilonova explosions). On October 19 an unusual small object designated A/2017 was detected by the Panoramic Survey Telescope and Rapid Response System or Pan-STARRS 1 telescope in Hawaii by a postdoctoral fellow, Rob Weryk, while searching for near earth objects for NASA. The motion of this body could not be explained as a normal asteroid or comet since it did not follow the normal orbits of near-earth objects but was on a hyperbolic trajectory crossing the ecliptic (plane of the planets) inside Mercury’s orbit and then made a hairpin turn due to the gravity of the sun under the earth’s orbit at the rapid speed of 27 miles/sec. Weryk and Karen Meech, an astronomer who studies small bodies possibly involved in solar system formation, both realized that this object probably came from another solar system around another star. Davide Farnocchia and Matt Holman,  scientists at NASA's Center for Near-Earth Object Studies (CNEOS) at the agency's Jet Propulsion Laboratory also concluded that the evidence suggested an interstellar origin!!! A graph of the orbit is shown in the following  UTube video
https://www.youtube.com/watch?v=uYBYrFJoL2E.

If this is true, this asteroid must have spent millions  if not billions of years traveling from another solar system to the earth. I find this discovery fantastic and exciting.

An astronomer friend of mine, Ben Zuckerman, reminded me that this type  of astronomical phenomenon makes the suggestion  of "panspermia" or "lithopanspermia" - that life arrived on earth from other planets or even from exoplanets in other solar systems - in the realm of possibility.

The Nevada Massacre

The massacre of over 50 people in a Nevada hotel by one man with an automatic rifle is due entirely to the Nevada gun laws or lack thereof. Nevada has some of the most relaxed gun laws in the United States. Firearm owners there are not required to have a license, and do not have to register their weapons. The state does not prohibit the sale of assault rifles, and places no limits on the number of firearms an individual can possess and the capacity of ammunition magazines.

The second amendment to the US Constitution states: "A well regulated Militia, being necessary to the security of a free State, the right of the people to keep and bear Arms, shall not be infringed." Since there are no longer any militias in this country as in the days when the US Constitution was being written, this clearly does not allow people to "keep and bear arms" as was interpreted by the Supreme Court in 2008 in the Heller decision and is used by the right wing as justification for the unlimited ownership of guns in this country.

This however was not the worst Supreme Court decision in our history. That goes to the Dred Scott decision in 1857 by the Taney Court. It has been said that this decision was characterized by "convoluted logic, tortured misreadings of key constitutional provisions, contempt of precedent, distortion of history, and judicial activism on a world-historical scale". It led eventually to the Civil War.

The Heller decision has led to the modern day gun lobby headed by the National Rifle Association or NRA and to this country being the most violent civilized country in the world. The NRA has not yet made its normal soothing statements about the holy American gun rights after the Nevada massacre, since it must first wash the blood off its hands.

Guns must be banned from our country as is the case in England and every other civilized country. There will be enough death and destruction in our country and in the world as climate warming gets worse, but the absence of guns in private hands will decrease the killing of innocent people.

It is Time...

For the sake of this country and the entire world, Trump must be removed as President of the United States. He is Commander in Chief of the military forces in this country and has the sole authority to launch nuclear weapons. Ponder that for a moment. We are relentlessly moving towards a military confrontation (=war) with North Korea, and Trump’s response is to threaten “fire and fury” and call the North Korean dictator schoolyard names such as Rocket Man and Little Rocket Man. Very recently there was an exciting news story that the United States had a “back channel” with North Korea which could possibly be used for negotiation, and Trump tells the Secretary of State “Don’t waste time talking to Little Rocket Man” and “Save your energy, Rex, we’ll do what has to be done”, a Trumpian way of saying that we will attack North Korea, thereby initiating World War III which almost certainly would involve the use of nuclear weapons. This is in spite of both China and Russia saying that they would intervene if the US attacked first and this intervention would almost certainly be militarily. Ponder that for a moment.

Trump is clearly mentally incapable of the duties of the

Presidency and is too dangerous to be allowed to be ”doing what has to be done.” Meanwhile, Trump is planning to attend a Golf Trophy Ceremony while at the same time sending horrible tweets to the Mayor of San Juan who had the courage to tell Trump that her people have no houses to live in, potable water to drink, electric power to communicate and fuel to run trucks and cars (and generators) from the recent hurricane. She said that her people are dying and that the US and Trump are killing them by their inefficiency and bureaucracy. The ghost writer of Trump’s “Art of the Deal” says that he is “deeply disturbed” and utterly “untrustworthy”. Add to that - belligerent, thin-skinned, unable to apologize for anything, a sexual predator, anti-science and a climate denier. But these pale against his threatening nuclear war.

Congress should create a commission to examine if the 25th

amendment should be invoked to replace Trump with the Vice President, Mike Pence, who is a religious nut case and a disciple of the Republican mantra of tax cuts for the wealthy and repeal of Obama Care, but not crazy enough to attack North Korea and use nuclear weapons.

I urge the Congress to do this as soon as possible and hopefully

prevent a third world war.

The Power Emergency in Puerto Rico - an Idea

The Class 4 -5 Hurricane Maria has apparently cut off all electronic communication with the outside world. There is only a single cell phone service and this is very fragile. The Governor has warned people not to expect restoration of the island’s electric grid possibly for several months.  Puerto Rico’s electric grid is 44 years old and the only power company, the Puerto Rico Electric Power Authority (PREPA), has recently declared bankruptcy and for some time has prevented or limited the development of solar power in the island, even though Puerto Rico is a tropical island and has more than 10-fold the extent of sunlight as, e.g. Miami, ignoring cloud cover.  

I have a suggestion that may speed up the restoration of power to the island and also at the same time act as a model system for the use of solar power in a new type of decentralized electric grid in general. I suggest that solar power should be installed on or adjacent to every house and business together with appropriate Tesla-like storage batteries. Of course, reconstruction of the structures is required before the solar panels can be situated. So, this is definitely a non-trivial exercise, but the reconstruction of houses and businesses (and the grid) must proceed in any case. Of course a grid expert must be involved in devising a novel type of “micro-grid” that would of allow total decentralization as well as installation of devices at each set of panels for easily removing  the panels from the grid. The benefit of this proposal is that electric power will be restored much more rapidly than simply replicating the old electric grid system and relying on centralized fossil fuel generation of power. And the most important benefit is that this will be a test of the possibility of decentralization that could be  used in other island disasters or even in mainland cities after extreme destruction, natural or man-made. One possible man-made disaster could  be EMP pulses created by explosion of nuclear weapons in the atmosphere.

I just discovered that there is now a possible commercial solution (Novagen) to the problem of installation of solar power in sites as exist now in Puerto Rico.

Rapid Roll "I" - Under Development (http://www.renovagen.com/products/rapid-roll-i/)(http://www.renovagen.com/products/rapid-roll-t/)

The integration of the Rapid Roll technology into a side-opening ISO shipping container, combined with inverters and a larger battery bank, creates an easily transportable self-sufficient solar power system capable of generating 10 times more power than competitive products. Deploying a huge solar array measuring 5 metres (20 ft ISO) or 10 metres (40 ft ISO) in width and up to 200 metres in length, this represents by far the largest containerized deployable solar array yet conceived. At this scale a multi-MW solar power plant could be deployed in a matter of hours – city-scale power sufficient for a large mining site or military main operating base.

Renovagen envisages that this technology could revolutionize the cost-effective and environmentally-friendly provision of large amounts of off-grid power in remote locations across many industries – including military, disaster relief, mining, oil & gas, construction, events and telecommunications. Indeed it has the potential to save lives by – for example, reducing or eliminating the need for military fuel convoys or by powering medical facilities in disaster zones.

An ISO container form factor utilizes existing transportation and container-handling infrastructure, but it may be sufficiently light-weight to be air-lifted by transport aircraft or heavy-lift helicopter. By integrating more efficient solar cells in the future, systems of up to 600kWp may become possible – for the first time mobilizing truly industrial scale solar power.

Rapid Roll "T"

The Rapid Roll “T” trailer/tactical version provides an extremely mobile solution which can be airlifted by a wide range of medium and heavy-lift helicopters (gross weight from 1,500 kg) but packs enough power for energy intensive operations. Easily mounted on an on-road or off-road trailer or flat-bed truck, the Rapid Roll “T” provides many options for deployment to practically any global location imaginable. With simple deployment in just a few minutes without needing solar engineers onsite, it provides a practical solution for humanitarian and disaster relief, military, mining, events, film production and other temporary power-hungry operations in remote places which require equipment mobility. The size and weight of the Rapid Roll “T” when trailerised (2,000kg – 3,000kg total trailer weight) also makes it easy to tow with standard 4×4 vehicles and it fits on a number of commercial air freight pallets or 463L military pallet and also becomes extremely easy to transport internationally very quickly. Easy handling is facilitated with bi-directional forklift pockets and lifting rings.

The Dossier(s)?

The Dossier(s)?

The prison bars are slowly closing around Trump. I hope fast enough to prevent a war with North Korea. Following are two recent articles about the infamous dossier, including the salacious portion.  I myself have been closely following the dossier investigation. One nice thing about the dossier is that in the published version someone used a yellow highlighter to emphasize the best parts (Perhaps the use of a yellow highlighter is an “in joke”). Although it is possibly leaning towards a type of  “schadenfreude” (Translation: “the experience of pleasure, joy, or self-satisfaction that comes from learning of or witnessing the troubles, failures, or humiliation of another”) but I just can’t help it with this numbnut (Translation: The stupidest of the stupid. A complete dumbass, one whose intelligence quotient does not surpass that of the average rock), but I myself have been pushing for more on the salacious portion of the dossier.

And now for two recent articles about the dossier:

 How's THIS for a bombshell? It comes from BBC World News Correspondent Paul Wood (and was published in THE SPECTATOR, a weekly UK magazine):

"Steele is not the only source [on the infamous "pee tape]. I heard of Russian "Kompromat" - compromising material- on Trump from two sources months before the Steele Dossier came to light. That might be evidence for Trump's statement that Russian intelligence, as well as the US agencies, are out to get him. There are, though, reports of witnesses in the hotel who corroborate Steel's reporting. These include an American who's said to have seen a row with hotel security over whether the (alleged) hookers would be allowed up to Trump's suite. The dossier's account of hookers in a Moscow hotel room was the subject of gossip among a select group of  journalists, politicians, and intelligence people for months before it was published. Now claims are circulating of  more tapes showing an even more extreme behavior. Expect these allegations to emerge in due course."

And of course the following BBC-published report from Paul Wood can't possibly be retweeted enough times.....

"Former MI6 agent, Christopher Steele, is not the only source for the claim about Russian Kompromat on the president-elect. Back in August, a retired head of an East European intelligence agency told me he had been informed of its existence by the "head of an East European intelligence Agency." Later I  used an intermediary to pass some questions to active duty CIA officers dealing with the case file - they would not speak to me directly. I got a message back that there was "more than one tape", "audio and video", on "more than one date", "in more than one place" - in the Ritz-Carlton in Moscow and also in St. Petersberg - and that the material [in the Trump tape held by the Kremlin] was "of a sexual nature"."

WOW!

Don’t forget to call your Congressperson and push for impeachment. Treason alone just won’t do it, but an old-fashioned  sex scandal just might.